1. Field of the Invention
The present invention relates to melanocortin receptors and more specifically to the treatment of sexual dysfunction using melanocortin receptor 3 ligands.
2. Background Information
Sexual dysfunction can be due to several physiological, as well as psychological, factors. In males, erectile dysfunction can be associated with diseases such as diabetes mellitus, syphilis, alcoholism, drug dependency, hypopituitarism and hypothyroidism. Erectile dysfunction can also be caused by vascular and neurogenic disorders, or be a side effect of drugs such as hypertensives, sedatives, tranquilizers and amphetamines. In all, erectile dysfunction is estimated to affect up to 10 million men in the United States, with its incidence increasing with age up to 25% of men at age 65.
While various pharmaceutical treatments are commercially available or being developed, the underlying physiological bases for sexual dysfunction are not well understood. Attention has recently been drawn to melanocortin (MC) receptors, which are a group of cell surface proteins that mediate a variety of physiological effects. The MC receptors have been implicated in the regulation of adrenal gland function such as production of the glucocorticoid cortisol and aldosterone, control of melanocyte growth and pigment production, control of feeding, thermoregulation, immunomodulation, inflammation and analgesia. Five distinct MC receptors have been cloned, although the specific role of each MC receptor is still unclear.
Certain compounds, termed xe2x80x9cmelanocortinsxe2x80x9d have been found to bind MC receptors, causing the activity of the receptors to increase or decrease. These melanocortins include melanocyte-stimulating hormones (MSH) such as xcex1-MSH, xcex2-MSH and xcex3-MSH, as well as adrenocorticotropic hormone (ACTH). Other compounds may bind as ligands to MC receptors, increasing or decreasing the activity of the receptors.
Thus, there is a need for compounds that can affect the activity of specific MC receptors that are involved with sexual dysfunction. The present invention satisfies this need and provides related advantages as well.
The present invention provides a method for treating sexual dysfunction, such as erectile dysfunction or sexual arousal disorder, with a compound having the generic formula X1xe2x80x94X2-(D)Phe-Arg-(D)Trp-X3. A particularly useful compound is HP-228, which has the formula Ac-Nle-Gln-His-(D)Phe-Arg-(D)Trp-Gly-NH2.
The invention also provides methods for selecting melanocortin receptor-3 ligands by determining whether a compound modulates the activity of MC-3 as an agonist or antagonist. These methods can be used to screen compound libraries for ligands to treat MC-3-associated conditions. Such conditions include sexual dysfunction, including erectile dysfunction and sexual arousal disorder.